Chromatin loop dynamics during cellular differentiation are associated with changes to both anchor and internal regulatory features.
Chromatin loop dynamics during cellular differentiation are associated with changes to both anchor and internal regulatory features.
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DOI：
10.1101/gr.277397.122
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发表时间：
2023-08
期刊：
影响因子：
7
通讯作者：
Phanstiel, Douglas H.
中科院分区：
文献类型：
--
作者：
Bond, Marielle L.;Davis, Eric S.;Quiroga, Ivana Y.;Dey, Anubha;Kiran, Manjari;Love, Michael I.;Won, Hyejung;Phanstiel, Douglas H.
三维（3D）染色质结构已被证明在生物转变期间调节基因转录中起作用。虽然我们对环的形成和维持的理解正在迅速提高，但对驱动环变化的机制以及差异环对基因转录的影响知之甚少。一个限制是缺乏功能强大的差分循环数据集。为了解决这个问题，我们进行了巨核细胞发育的深度测序Hi-C时间过程，包括每个时间点的四个生物学重复和60亿个读取。统计学分析显示1503个微分环。获得的环锚富集AP-1占据，其特征在于组蛋白H3 K27 ac的大幅增加（超过11倍），但CTCF和RAD 21结合的相对较小的增加（分别为1.26和1.23倍）。线性模型显示，组蛋白H3 K27 ac、染色质可及性和JUN结合的变化与成环的变化的相关性比RAD 21更好，并且几乎与CTCF一样相关。表观遗传特征之间的变化，而不是在边界是高度预测循环的变化。总之，这些数据表明，虽然CTCF和RAD 21可能是决定环形成的核心机制，但其他特征（在锚点和环边界内）可能在确定细胞类型和条件的相对环强度方面发挥比先前预期更大的作用。
Three-dimensional (3D) chromatin structure has been shown to play a role in regulating gene transcription during biological transitions. Although our understanding of loop formation and maintenance is rapidly improving, much less is known about the mechanisms driving changes in looping and the impact of differential looping on gene transcription. One limitation has been a lack of well-powered differential looping data sets. To address this, we conducted a deeply sequenced Hi-C time course of megakaryocyte development comprising four biological replicates and 6 billion reads per time point. Statistical analysis revealed 1503 differential loops. Gained loop anchors were enriched for AP-1 occupancy and were characterized by large increases in histone H3K27ac (over 11-fold) but relatively small increases in CTCF and RAD21 binding (1.26- and 1.23-fold, respectively). Linear modeling revealed that changes in histone H3K27ac, chromatin accessibility, and JUN binding were better correlated with changes in looping than RAD21 and almost as well correlated as CTCF. Changes to epigenetic features between—rather than at—boundaries were highly predictive of changes in looping. Together these data suggest that although CTCF and RAD21 may be the core machinery dictating where loops form, other features (both at the anchors and within the loop boundaries) may play a larger role than previously anticipated in determining the relative loop strength across cell types and conditions.
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影响因子：
10.5
作者：
Karr JP;Ferrie JJ;Tjian R;Darzacq X
通讯作者：
Darzacq X
相位分离驱动异常的染色质循环和癌症发展。
影响因子：
64.8
作者：
Ahn JH;Davis ES;Daugird TA;Zhao S;Quiroga IY;Uryu H;Li J;Storey AJ;Tsai YH;Keeley DP;Mackintosh SG;Edmondson RD;Byrum SD;Cai L;Tackett AJ;Zheng D;Legant WR;Phanstiel DH;Wang GG
通讯作者：
Wang GG
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B
影响因子：
30.8
作者：
Fulco, Charles P.;Nasser, Joseph;Engreitz, Jesse M.
通讯作者：
Engreitz, Jesse M.
影响因子：
64.5
作者：
Gasperini, Molly;Hill, Andrew J.;Shendure, Jay
通讯作者：
Shendure, Jay